Cyanoalkyl substituted-3-oxo-alkamidines

ABSTRACT

The present invention relates to amidino ketones, which are useful as hypoglycemic agents, having the formula   WHEREIN R1 is alkyl of 1 to 4 carbon atoms, phenyl or substituted phenyl, R2 is alkyl of 1 to 4 carbon atoms, or R1 and R2 together are -(CH2)n-, wherein n is an integer from 2 to 7, and R3 is alkyl of 1 to 4 carbon atoms, or R1, R2 and R3 together with the carbon atom to which they are bound form the adamantyl radical, R4 is alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkoxyalkyl of 2 to 8 carbon atoms in the aggregate thereof, cyanoalkyl wherein the alkyl radical is of 1 to 5 carbon atoms, or a group of formula   WHEREIN R7 and R8 are the same or different and each is alkyl of 1 to 4 carbon atoms, and R5 and R6 are the same or different and each is alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkoxyalkyl of 2 to 8 carbon atoms in the aggregate thereof or cyanoalkyl wherein the alkyl is of 1 to 5 carbon atoms, or one of R4, R5 and R6 is phenyl or substituted phenyl and the others of R4, R5 and R6 are as defined above, provided at least one of R4, R5 and R6 is cyanoalkyl wherein the alkyl is of 1 to 5 carbon atoms.

United States Patent 91 Heffe 1 Apr. 1,1975

CYANOALKYL SUBSTlTUTED-3-OXO-ALKAMIDINES [75] Inventor: Wilhelm Heffe, Neuenegg,

Switzerland [73] Assignee: Sandoz-Wander Inc., Hanover, NJ.

[22] Filed: June 4, 1973 [21] Appl. No.: 366,681

[30] Foreign Application Priority Data June 7, 1972 Switzerland 8443/72 Feb. 28, 1973 Switzerland 2917/73 [52] U.S. Cl. 260/465.5 R, 260/247.1, 260/247.5 R, 260/293.73, 260/293.75, 260/293.78, 260/293.79, 260/293.85, 260/293.87, 260/307 F, 260/326.5 S, 260/326.5, 260/464, 260/465 D, 260/465 E, 260/465.4, 424/248, 424/267, 424/272, 424/304 [51] Int. Cl. C07c 121/42, C07c 121/66 [58] Field of Search 260/465.5 R, 464, 465 E [56] References Cited UNITED STATES PATENTS 2,850,521 9/1958 Mower 260/464 X 3,055,883 9/1962 260/465.5 X 3,093,632 6/1963 Mull 260/465.S X 3,119,735 l/1964 Gubler et a1 260/465.7 X 3,202,710 8/1965 Bolger 260/464 X 3,203,988 8/1965 Campbell 260/464 X 3,234,266 2/1966 Blanchard, Jr 260/464 X 3,270,054 8/1966 Gagneux et al 260/464 X 3,283,003 11/1966 Jack 260/464 X ABSTRACT The present invention relates to amidino ketones,

which are useful as hypoglycemic agents, having the R, is alkyl of 1 to 4 carbon atoms, phenyl or substituted phenyl,

R is alkyl of l to 4 carbon atoms, or

R and R together are (Cl-1 wherein n is an integer from 2 to 7, and

R is alkyl of 1 to 4 carbon atoms, or

R R and R together with the carbon atom to which they are bound form the adamantyl radical,

R is alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkoxyalkyl of 2 to 8 carbon atoms in the aggregate thereof, cyanoalkyl wherein the alkyl radical is of 1 to 5 carbon atoms, or a group of formula wherein R and R are the same or different and each is alkyl of l to 4 carbon atoms, and

R,-, and R are the same or different and each is alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkoxyalkyl of 2 to 8 carbon atoms in the aggregate thereof or cyanoalkyl wherein the alkyl is of l to 5 carbon atoms, or one of R R and R is phenyl or substituted phenyl and the others of R R and, R are as defined above, provided at least one of,R R and R is cyanoalkyl wherein the alkyl is of 1 to 5 carbon atoms.

8 Claims, No Drawings CYANOALKYL' SUBSTITUTED-S-OXO-ALKAMIDI-NES IMPROVEMENTS IN OR RELATING TO ORGANIC COMPOUNDS The present invention relates to amidino ketones, especially 3-oxo-butanamidine derivatives.

The invention provides compounds of formula I,

wherein R is alkyl of 1 to 4 carbon atoms,

tuted phenyl, and

R is alkyl of l to 4 carbon atoms, or

R and R together are -(CI-I wherein n is an integer from 2 to 7,

and

R is alkyl of l to 4 carbon atoms, or

R R and R together with the carbon atom to which they are bound form the adamantyl radical,

R is alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkoxyalkyl of 2 to 8 carbon atoms in the aggregate thereof, cyanoalkyl wherein the alkyl radical is of l to 5 carbon atoms, or a group of formula phenyl or substiwherein R, and R are the same or different and each is alkyl of l to 4 carbon atoms, or

R and R together with the nitrogen atom are a heterocyclic ring, or a heterocyclic ring having a ring oxygen atom, and

R and R are the same or different and each is alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkoxyalkyl of 2 to 8 carbon atoms in the aggregate thereof or cyanoalkyl wherein the alkyl is of l to 5 carbon atoms, or one of R R and R is phenyl or substituted phenyl and the others of R R and R are as defined above.

When in formula I R or one of the substituents R R and R is a substituted phenyl group, the substituted phenyl group preferably is alkylphenyL'the alkyl radical having from 1 to 4 carbon atoms, especially methylphenyl, the alkyl substituent being preferably in the p position, or halophenyl, especially chlorophenyl, the.

halo substituent being preferably in the p position.

When R and R together with the nitrogen atom are a heterocyclic ring, this is preferably a five or six membered heterocyclic ring, preferably saturated e.g. morpholine, pyrrolidine or piperazine. f

Further, in accordance with the invention a compound of formula I may be obtained by a process comprising desulphurizing a compound of formula II,

R l yN R R -C-CO-CH S-C R 3 N 5 II wherein R to R are as defined above.

The process according to the invention may be effected in the presence of a desulphurizing agent, preferably triaryl derivatives, trialkyl derivatives or mixed alkyl/triaryl derivatives wherein each of the alkyl groups preferably is of 1 to 4 carbon atoms, of phosphorous, arsenic, antimony or bismuth, especially, however, of phosphorous or arsenic. Especially preferred are the phosphorus derivatives. Preferred examples of desulphurizing agents are triphenylphosphine or arsine and triethyl-phosphite.

The process according to the invention may be effected in the absence of a solvent or in an inert organic solvent, e.g. dimethyl formamide, dioxane or dimethyl acetamide. However, the reaction is preferably effected in the absence of a solvent. The reaction temperature may be from to C. After the reaction is complete, the reaction mixture may be acidified, e.g. with an acid capable of forming a water-soluble acid addition form of the compound of formula I, e.g. hydrobromic acid, the residue is conveniently filtered off and the resulting acid addition salt form of the compound of formula I is conveniently isolated from the resulting reaction mixture in known manner, e.g. by concentrating by evaporation, and may be purified, e.g. by recrystallization.

Free base forms of compounds of formula I may be converted into acid addition salt form in conventional manner, and vice versa.

Examples of suitable acids for acid addition salt formation are the hydrohalic acids such as hydrochloric and hydrobromic acid, or perchloric acid, and organic acids such as oxalic acid and maleic acid.

The compounds of formula 11, used as starting materials in the above process, may be obtained by reacting a reactive ester of an alcohol of formula Ill,

R -O-CO-CH OH III wherein R to R are as defined above, with a compound of formula IV,

N S-C R4 N\ R6 wherein R to R are as defined above.

Suitable reactive esters of the alcohol of formula III, include esters of hydrohalic acids, e.g. hydrobromic or hydrochloric acid, or the tosylate. The reaction may be effected either in the absence of a solvent or in an inert organic solvent, e.g. a lower alcohol of l to 6 carbon atoms, acetone, or a cyclic or straight chain ether such as dioxane, tetrahydrofuran or diisopropyl ether. The reaction temperature conveniently is from 20 to 100C. Free base forms of the resulting compounds of formula II are liberated from the acid addition salt forms in known manner, e.g. by treatment with an aqueous alkali metal hydroxide solution.

The compounds of formulae III and IV, used as starting materials in the above process, are either known or may be produced in known manner from known starting materials, for example a compound of formula IV wherein R R and R are alkyl may be obtained by reacting an alkvlisothiocyanate with a dialkyl amine in conventional manner.

In so far as the production of the starting material is not particularly described, these compounds are known or may be produced and purified in accordance The compounds of formula I are useful because they possess pharmacological activity in animals. In particular the compounds are useful as hypoglycaemic agents as indicated by a lowering of the blood sugar content in the blood of rats on p.o. administration of from 100 to 300 mg/kg animal body weight, of the compounds, in accordance with the following test:

The compound to be tested is administered in increasing doses to groups of 5 to 10 animals. 2 hours after administration, a blood sample is taken from each animal, and the glucose content in the blood serum is established using the ferric cyanide test. The blood sugar lowering effect is determined by a comparison with a control group of 5 to 10 animals to which is administered a physiological common salt solution.

For the above mentioned use the dosage will, of course, vary depending on the compounds employed, mode of administration and condition to be treated. However, in general, satisfactory results are obtained when administered at a daily dosage of from 1.5 mg to about 300 mg per kg animal body weight, conveniently given in divided doses 2 to 4 times a day or in sustained release form. For the larger mammals, the total daily dosage is in the range from about 100 to about 1000 mg, and dosage forms suitable for oral administration comprise from about 25 mg to about 500 mg of the compounds admixed with a solid or liquid pharmaceutical carrier or diluent.

As the free base forms of the compounds of formula I are usually oily at room temperature, the compounds are conveniently administered in pharmaceutically acceptable acid addition salt forms which have the same order of activity as the free base forms, and which are readily prepared in conventional manner. Representative acid addition salt forms include organic acid salt forms such as the hydrogen maleate, fumarate, tartrate and methane sulphonate and mineral acid salt forms H IV;

such as the hydrochloride, hydrobromide and sulphate. A pharmacetical composition may comprise a compound of formula I, in free base form or in pharmaceutically acceptable acid addition salt form, in association with a pharmaceutical carrier or diluent. Such compositions may be prepared by conventional techniques to be in the form of, for example, capsules, tablets, suppositories, suspensions or solutions, for enteral or parenteral administration. Aside from the usual pharmaceutical diluents or carriers, e.g. water, alcohols, natural or hardened oils and waxes, these pharmaceutical compositions may contain suitable preserving, stabilizing, wetting, solubilizing, sweetening, flavouring or colouring agents.

An example of a tablet composition comprises 136 mg of N-butyl-N ,N -diallyl-4,4-dimethyl-3-oxopentanamidine hydrobromide, 1 mg of magnesium stearate, 4 mg of polyvinyl pyrrolidone, 0.5 mg of dimethyl silicone oil, 5 mg of talc, 10 mg of maize starch, 137.8 mg of lactose and 1.5 mg of polyethylene glycol 6000.

The tablets are produced in conventional manner and are provided with a double slit.

In a preferred class of compounds, R R and R are independently alkyl, R, is alkyl, alkenyl, phenyl, or substituted phenyl and R and R are, independently, alkyl, alkenyl, alkoxyalkyl or cyanoalkyl. More especially R R and R are alkyl, especially methyl, and R R and R are independently alkenyl especially of 3 to 4 carbon atoms or especially alkyl of l to 4 carbon atoms.

In another preferred class of compounds R and R are identical.

In another class of compounds R is phenyl or substituted phenyl and R is alkyl, or R and R together are -(CH and R is alkyl, or R R and R together with the carbon atom to which they are bound form the adamantyl radical, R is a group of formula;

wherein R, and R are the same or different and each is alkyl of l to 4 carbon atoms, or

R and R together with the nitrogen atom are a het- EXAMPLE 1 N ,N -triethyl-4,4-dimethyl-3-oxo-pentanamidine a. N,N -triethyl-5,5-dimethyl-4-oxo-2- thiahexanamidine A mixture of 14.3 g of bromopinacoline, 12.8 g of N,N-triethyl thiourea and 120 cc of acetone is heated to the boil at reflux for 8 hours. The reaction mixture is subsequently concentrated by evaporation in a vacuum. cc of an aqueous l N sodiumhydroxide solution are added to the resulting residue, and the resulting mixture is extracted with diethyl ether. The ethereal solution is dried with potassium carbonate and is subsequently concentrated by evaporation. N ,N -triethyl- 5,5-dimethyl-4-oxo-2-thiahexanamidine is obtained as hexanamidine hydrobromide i 19.5 g of N ,N -di-isobutyl-N -methyl thiourea are dissolved in. 100 cc of acetone, and 17.3 g of bromopinacoline are added to the solution. The resultoily residue. 5 ing mixture is allowed to stand at 20for 12 hours. The b. N,N -trlethyl-4,4-dimethyl-3-oxo-pentanamidine mixture is subsequently heated to the boil for 4 hours, g 0f the y thyl-5,5-dimethy1-4-0xois subsequently cooled, and the resulting precipitate is 2-thiahexanamidine obtained in section a) are mixed filtered off. The N ,N"-di-isobutyl-4-oxo-2-thia-N ,5,5- with 13.5 g of triphenyl phosph ne, and the mixture is trimethylhexanamidine hydrobromide, obtained as filheated in an oil bath to 120 for 6 hours in a flask proter residue, has a MP. of 202-204. vided with an upright tube. The reaction mixture is subc. N ,N -di-isobutyl-N,4,4-trimethyl-3-oxosequently cooled and triturated with 1 N hydrobromic pentanamidine acid until the acid reaction is maintained. The undis- 11.8 g of N ,N -di-isobutyl-4-oxo-2-thia-N,5,5- solved triphenyl phosphine sulphide is filtered off and trimethyl-hexanamidine (obtained from the hydrobrowashed with water. The aqueous filtrate is extracted mide by treatment with caustic soda solution and exwith diethyl ether and purified with charcoal. After the traction of the liberated base with ether) are heated to charcoal is filtered off, the aqueous filtrate is evapo- 120 for 8 hours together with 12.5 g of triphenyl arrated to dryness in a vacuum. After recrystallization sine. The resulting melted material is neutralized with from 2 parts by volume of isopropanol/g of compound, 1 N hydrobromic acid (about 28 cc). The aqueous soor from 4.5 parts by volume of acetone/g of compound, lution is poured off and cold alcohol is added to the the resulting N,N -triethyl-4,4-dimethyl-3-oxosmeary crystalline product until the solid components pentanamidine hydrobromide has a M.P. of 138-140. are filterable. Filtration is subsequently effected. The

Treatment of the hydrobromide with an aqueous 2 N filter residue contains about 11.6 g of a mixture of trisodium hydroxide solution, extraction of the alkaline phenyl arsine and triphenyl arsine sulphide. The filtrate solution with diethyl ether and concentration by evapois extracted with 100 cc of diethyl ether, and the aqueration of the ethereal mixture yields oily N ,N -triethyl- 0115 ution is concentrated by evaporation in a vac- 4,4-dimethyl-3-oxo-pentanamidine. uum. The evaporation residue is heated to 80 together with 150 cc of ethyl acetate, whereby after initial solution crystals are formed. Cooling is then effected to 0 EXAMPLE 2 Y and the residue N ,N -d1-lsobutyl-N ,4,4-tr1methyl-3- oxoentamidine h drobromide M.P. 151-156 is N ,N -d1-lsobutyl-N,4,4-trlmethyl-3-oxop y t filtered off. pen anaml The compounds of formula 1, indicated in the followa. N ,N -di-isobutyl-N-methyl thiourea ing Tables, are obtained by using the processes exem- A solution of 7.3 g of methyl isothiocyanate in 20 cc plified in the above Examples 1 and 2 and the correof benzene is added to a solution of 12.9 g of disponding starting materials. The indicated melting isobutylamine in cc of benzene, and the resulting points refer to the corresponding salt forms. The free mixture is allowed to stand at 20 for 4 days. The mixbase forms of the compounds of formula 1 are obtained ture is subsequently concentrated by evaporation, and from the salt forms in known manner, e.g. by treatment y N-m hyl hi ure having a MP. of 40 with caustic soda solution and extraction with ether. 98-100, is obtained as residue. i The substituents are in the (ti-position except where b. N ,N -di-isobutyl-4-oxo-2-thia-N,5,S-trimethylotherwise stated.

Example R1 R2 R3 R1 R5 R6 M.P. Salt form 3 Methyl Methyl Methyl Methyl Methyl Methyl 197-1 99 Bromide 4 Methyl Methyl Methyl Methyl Methyl Ethyl 174-1 Bromide 5 Methyl Meth l Methyl Methyl Ethyl Ethyl -167 Bromide 6 Methyl Methyl Methyl Methyl CH O-ethyl CH O-ethyl l30-131 Bromide 7 Methyl Methyl Methyl Methyl Propyl Propyl 1 77 Bromide 8 Methyl Methyl Methyl Methyl lsopropyl lsopropyl 160-161 Bromide 9 Methyl Methyl Methyl Methyl Allyl Allyl 8890 Bromide lo Methyl Methyl Methyl Methyl Butyl Butyl 119-120 Bromide 1 1 Methyl Methyl Methyl Methyl lsobutyl lsobutyl 155- 1 57 Bromide l 2 Methyl Methyl Methyl Ethyl Methyl Methyl -1 92 Bromide l 3 Methyl Methyl Methyl Ethyl Methyl Ethyl 144-145" Bromide l4 Methyl Methyl Methyl Ethyl CH O-ethyl CH O-ethyl 9 1 -93 Oxalate 1 5 Methyl Methyl Methyl Ethyl Propyl Propyl 143- 1 45 Bromide l6 Methyl Methyl Methyl Ethyl lsopropyl lsopropyl 1 32-1 34 Bromide l7 Methyl Methyl Methyl Ethyl Butyl Butyl 121-122 Bromide 1 8 Methyl Methyl Methyl Ethyl lsobutyl lsobutyl 160-1 62 Bromide l9 Methyl Methyl Methyl Ethyl Allyl Allyl 1 19-1 21 Bromide 20 Methyl Methyl Methyl Propyl Methyl Methyl 125-1 27 Bromide 21 Methyl Methyl Methyl Propyl Ethyl Ethyl 125-127 Bromide 22 Methyl Methyl Methyl Propyl CH O-ethyl CH O-ethyl 5456 Bromide 23 Methyl Methyl Methyl Propyl Propyl Propyl 10 l- 1 02 Bromide 24 Methyl Methyl Methyl Propyl lsopropyl lsopropyl 137-138 Bromide 25 Methyl Methyl Methyl Propyl lsobutyl lsobutyl 169-1 70 Bromide 26 Methyl Methyl Methyl Propyl Allyl Allyl 102-104 Oxalate 27 Methyl Methyl Methyl lsopropyl Ethyl Ethyl 151-152 Bromide 28 Methyl Methyl Methyl lsopropyl Propyl Propyl l l9-120 Bromide 29 Methyl Methyl Methyl lsopropyl lsopropyl lsopropyl l7 1-172 Bromide 30 Methyl Methyl Methylwe --lsopr0pyl Allyl Allyl 126-1 28 Oxalate 3 1 Methyl Methyl Methyl Allyl Methyl Methyl 140-1 42 Bromide 32 Methyl Methyl Methyl Allyl Ethyl Ethyl 136-1 37 Bromide 3 3 Methyl Methyl Methyl Allyl Propyl Propyl 140-1 41 Bromide 34 Methyl Methyl Methyl Allyl lsopropyl lsopropyl 140-142 Bromide Continued Example R R R R R R M.P. Salt form Methyl Methyl Methyl Allyl lsobutyl lsobutyl 148-149 Bromide 36 Methyl Methyl Methyl Allyl All 1 All 1 93-94 Oxalate 37 Methyl Methyl Methyl Butyl Met yl Me't yl 113-1 14 Bromide 38 Methyl Methyl Methyl Butyl Ethyl Ethyl 1l7-l 18 Bromide 39 Methyl Methyl Methyl Butyl Propyl Propyl 79-80" Bromide 40 Methyl Methyl Methyl Butyl lsopropyl lsopropyl 130-1 32 Bromide 41 Methyl Methyl Methyl Butyl Butyl Butyl 78-8 2 Bromide 42 Methyl Methyl Methyl Butyl Allyl Allyl 80-81 Bromide 43 Methyl Methyl Methyl lsobutyl Ethyl Ethyl 192-1 94 Bromide 44 Methyl Methyl Methyl lsobutyl Propyl Propyl 103-1 04 Bromide 45 Methyl Methyl Methyl lsobutyl Allyl Allyl 96-98 Bromide 46 Methyl Methyl Methyl sec-Butyl Ethyl Ethyl 128-1 3 1 Bromide 47 Methyl Methyl Methyl sec-Butyl CH O-ethyl CH O-ethyl 83-84 Oxalate 48 Methyl Methyl Methyl sec-Butyl Propyl Propyl l l3-1 14 Oxalate 49 Methyl Methyl Methyl sec-Butyl Allyl Allyl 104-105 Oxalate 50 Methyl Methyl Methyl ten-Butyl Ethyl Ethyl 138-1 39 Bromide 5 1 Methyl Methyl Methyl tert-Butyl lsopropyl lsopropyl 134-1 35 Bromide 52 Methyl Methyl Methyl Amyl Methyl Methyl 128-1 30 Bromide 53 Methyl Methyl Methyl i Amyl Ethyl Ethyl 74-76 Oxalate 54 Methyl Methyl Methyl Amyl Propyl Propyl 60-61 Bromide 55 Methyl Methyl Methyl Amyl Allyl Allyl 82-84 Oxalate 56 Methyl Methyl Methyl lsoamyl Ethyl Ethyl 1 19-1 20 Bromide 57 Methyl Methyl Methyl Octyl Ethyl Ethyl 84-85 Bromide 58 Methyl Methyl Ethyl Ethyl Ethyl l07l09 Bromide 59 Methyl Methyl Ethyl Methyl lsobutyl lsobutyl 143-145" Bromide 60 Methyl Methyl Ethyl Ethyl Propyl Propyl 125-126 Oxalate 6 1 Methyl Methyl Ethyl Ethyl Allyl Allyl 87-8 8 Oxalate 62 Methyl Methyl Ethyl sec-Butyl Ethyl Ethyl 100-102 Bromide 63 Methyl Methyl Methyl Methyl Methyl Phenyl 1 89-1 92 Bromide 64 Methyl Methyl Methyl Ethyl Ethyl Phenyl 21 3-216 Bromide 65 Methyl Methyl Methyl Phenyl Methyl Methyl 179-1 82 Bromide 66 Methyl Methyl Methyl Phenyl Ethyl Ethyl 169-1 72 Bromide 67 Methyl Methyl Methyl Phenyl Propyl Propyl 181-1 82 Bromide 68 Methyl Methyl Methyl Phenyl Allyl Allyl 1 13-1 15 Bromide 69 Methyl Methyl Methyl p-Cl-phenyl Ethyl Ethyl 18 1-183 Bromide 70 Methyl Methyl Methyl p-CH -phenyl Ethyl Ethyl 162-1 63 Bromide 7 1 Methyl Methyl Phenyl Ethyl Ethyl Ethyl 143-144 Bromide 72 Methyl Methyl Ethyl Butyl Ethyl Ethyl 1 13-1 14 Bromide 73 Methyl Methyl Ethyl sec-Butyl Allyl Allyl 9293 Oxalate 74 Methyl Methyl Methyl sec-Butyl lsopropyl Isopropyl 1 63-1 64 Bromide 75 Methyl Methyl Methyl Octyl Methyl Methyl 127-1 28 Bromide 76 Methyl Methyl Methyl B-Methallyl Meth l Meth l 135-137 Bromide 77 Methyl Methyl Methyl B-Methallyl Ethy Ethy 15 3-] 55 Bromide 7 8 Methyl Methyl Methyl }8Methally1 Propyl Propyl 142143 Bromide 79 Methyl Methyl Methyl Hexyl Ethyl Ethyl 90-9 1 Oxalate 80 Methyl Methyl Methyl Butyl Methyl Ethyl 108-109 Bromide 8 1 Methyl Methyl Methyl Hexyl Methyl Methyl 128-129 Bromide 82 Methyl Methyl Methyl lsobutyl Methyl Meth l 185-186 Bromide 83 Methyl Methyl Methyl sec-Butyl Methyl Ethy 98-100 Bromide 84 Methyl Methyl Methyl tert-Butyl Methyl Ethyl 163-1 64 Bromide 85 Methyl Methyl Methyl sec-Hexyl Methyl Methyl 8 1-8 2 Oxalate 86 Methyl Methyl Methyl Methyl lsoam l lsoam 1 164-165 Bromide 87 Methyl Methyl Methyl lsoamyl All Ally 74-75 Oxalate 88 Methyl Methyl Methyl sec-Hexyl Met yl Ethyl 108-1l0 Oxalate 89 Methyl Methyl Methyl Ethyl Z-Cyanoethyl 2-cyanoethyl 167-1 68 Bromide 90 Methyl Methyl Methyl sec-Butyl Methyl 2-cyanoethyl -96 Oxalate Using the process exemplified in Example 1 or 2 and the appropriate starting materials, there are obtained the following compounds Structure: I

N- [CB 2 .0. [Cl-1 1 .CH

CH -C CO .Ci-l -C 1 CH CH 65 What is claimed is: l. A compound of the formula R,, R, and R, together with the carbon atom to which I they are bound form the adamantyl radical,

R, is alkyl of l to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, alkoxyalkyl of 2 to 8 carbon atoms in the aggregate thereof, cyanoalkyl wherein the alkyl radical is of l to 5 carbon atoms, or a group of formula wherein R-, and R, are the same or different and each is alkyl of l to 4 carbon atoms, and

R, and R, are the same or different and each is alkyl of 1 to 8 carbon atoms, alkenyl of 2'to 8 carbon atoms, alkoxyalkyl of 2 to 8 carbon atoms in the aggregate thereof or cyanoalkyl wherein the alkyl is of 1 to 5 carbon atoms, or one of R,, R, and R, is phenyl or phenyl substituted with alkyl of 1 to 4 carbon atoms or halo and the others of R,, R, and R, are as defined above, provided at least one of R,, R, and R, is cyanolkyl wherein the alkyl is of i to 5 carbons.

2. A compound of claim 1, wherein R, or one of R,, R, and R, is, when substituted phenyl, alkylphenyl, the alkyl radical thereof having 1 to 4 carbon atoms, or halophenyl. t

3. A compound of claim 1, wherein R,, I and R, are methyl.

4. The compound of claim 3, wherein R, is ethyl, R, is Z-eyanoethyl, R, is Z-cyanoethyl.

5. The compound of claim 3, wherein R, is sec-butyl, R, is methyl and R, is Z-cyanoethyl.

6. A compound of claim 1, wherein R, and R, are methyl and R, is ethyl.

7. A compound of the formula,

wherein R, to R, and the proviso are as stated in claim 1! I 8. A compound according to claim 1 having the structure R is alkyl of 1 to 4 carbon atoms, phenyl or phenyl substituted with alkyl of l to 4 carbon atoms or chloro, and

R, is alkyl of 1 to 4 carbon atoms, or

R, and R, together are (CH,),,, wherein n is an integer from 2 to 7, and

R, is alkyl of 1 to 4 carbon atoms, or

R,, R, and R, together with the carbon atom to which they are bound form the -adamantyl radical,

R, is alkyl of l to 8 carbon atoms, alkenyl of 3 to 4 carbon atoms, methoxyethyl or cyanoethyl or a group of formula wherein R, and R, are the same or different and each is alkyl of l to 4 carbon atoms, and

R, and R, are the same or different and each is alkyl of i to 8 carbon atoms, alkenyl of 3 to 4 carbonatoms, methoxyethyl or cyanoethyl, or one of R,, R, and R, is phenyl or phenyl substituted with alkyl of 1 to 4 carbon atoms or chloro and the others of- R,, R, and R, are as defined above,

provided at least one of R,, R, and R, is cyanoethyl.

i l i I I 

1. A COMPOUND OF THE FORMULA
 2. A compound of claim 1, wherein R1 or one of R4, R5 and R6 is, when substituted phenyl, alkylphenyl, the alkyl radical thereof having 1 to 4 carbon atoms, or halophenyl.
 3. A compound of claim 1, wherein R1, R2 and R3 are methyl.
 4. The compound of claim 3, wherein R4 is ethyl, R5 is 2-cyanoethyl, R6 is 2-cyanoethyl.
 5. The compound of claim 3, wherein R4 is sec-butyl, R5 is methyl and R6 is 2-cyanoethyl.
 6. A compound of claim 1, wherein R1 and R2 are methyl and R3 is ethyl.
 7. A compound of the formula,
 8. A compound according to claim 1 having the structure 